Saline Infusion Through the Pancreatic Duct Leads to Changes in Calcium Homeostasis Similar to Those Observed in Acute Pancreatitis

Abstract

This work focuses on studying the early events associated with pancreatic damage after retrograde infusion through the pancreatic duct in rats. We have analyzed changes in calcium homeostasis and secretory response in pancreatic acini from rats with taurocholate-induced acute pancreatitis. Moreover, in order to test whether pancreatic duct manipulation can trigger damage inside pancreatic acinar cells, we have studied both parameters in acini from animals infused with saline. Our study demonstrates that taurocholate causes evident damage to acinar cells, impairing both calcium homeostasis and secretory response to CCK. In saline, a significant decrease in calcium cytosolic response to CCK was observed. Calcium disturbances similar to those observed in acute pancreatitis appear before secretion blockade and inflammation processes in saline treated rats. These results could be interesting since pancreatitis is associated to clinical procedures that require duct manipulation such as endoscopic retrograde cholangiopancreatography.

Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis

“…Moreover, an important reduction in calcium response to cholecystokinin is also observed in rats with AP ( Figure 1B) [20,21] . Calcium signalling alteration seems to be one of the earliest events in AP development since it is observed previous to enzy matic secretion impairment in pancreatic acini [21] . Sustained elevation of cytosolic Ca 2+ , described as occurring during the onset of AP, depend on both release of Ca 2+ from intracellular stores and uptake from the extracellular milieu [2224] .…”

“…Unregulated activation of pancreatic enzymes is related to an impaired cytosolic Ca 2+ homeostasis [18,19] . Thus, we have demonstrated, by using two different AP experimental models [20,21] , that basal levels of cytosolic Ca 2+ are significantly increased in pancreatic acini isolated from pancreatitic rats with respect to control animals ( Figure 1A). Moreover, an important reduction in calcium response to cholecystokinin is also observed in rats with AP ( Figure 1B) [20,21] .…”

“…Thus, we have demonstrated, by using two different AP experimental models [20,21] , that basal levels of cytosolic Ca 2+ are significantly increased in pancreatic acini isolated from pancreatitic rats with respect to control animals ( Figure 1A). Moreover, an important reduction in calcium response to cholecystokinin is also observed in rats with AP ( Figure 1B) [20,21] . Calcium signalling alteration seems to be one of the earliest events in AP development since it is observed previous to enzy matic secretion impairment in pancreatic acini [21] .…”

“…SP has been detected within the pancreas and its levels are increased in caerulein induced AP [38] . Moreover, we have recently shown that both neurotransmitters, SP and CGRP, are massively released from sensitive fibers within the pancreas of rats with taurocholateinduced SAP [21] suggesting that neurogenic inflammation is important in SAP development.…”

Risk Factors for Worsening of Acute Pancreatitis in Patients Admitted with Mild Acute Pancreatitis

“…Calcium level has been used as a predictor of the severity of acute pancreatitis for quite a long time, and it was included in the Ranson criteria established in 1977 [8]. It is known that disturbances of intracellular calcium homeostasis, characterized by high cytosolic calcium concentration in the pancreatic acinar cells, are involved in the pathophysiology of the onset of acute pancreatitis [24]. Therefore, although serum calcium level on admission might be correlated with severity of AP on admission, it was not found to be a risk factor for progression to more severe pancreatitis in our study.…”